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Kleine-Levin syndrome is a rare sleep disorder of unknown etiology characterized by repetitive episodes of hypersomnia between asymptomatic periods. We report the case of a 13-year-old girl who presented with drowsiness triggered by influenza A as the first episode. Magnetic resonance imaging (MRI) on day 6 showed transient reduction of diffusion in the corpus callosum splenium. The patient was diagnosed with encephalopathy with a reversible splenial lesion. The symptoms resolved after 10 days, but additional episodes of hypersomnia lasting 5-10 days occurred 1, 5, 6, 11, 13, and 25 months after the first episode. MRI during hypersomnia indicated no lesions, and sleep duration and cognition were normal between episodes. The patient was diagnosed with Kleine-Levin syndrome. Electroencephalographic and clinical findings during the first episode were similar to those during the other episodes. Encephalopathy with a splenial lesion and Kleine-Levin syndrome may have similar pathological mechanisms causing a disturbance in consciousness.

Civil service employee pension reform began by removing non-clerical work from the main body of the Mutual Aid Association (MAA) pension system. Further changes were based on administrative reform and pension jealousy. In particular, the Nakasone cabinet's administrative reform privatized the non-clerical sector. Before the 1979 reform, the pensionable age was 55 for the MAA and 60 for the Employee Pension Insurance (EPI) scheme. The MAA pension benefit formula adopted the final salary system, which was larger than the average lifetime salary calculation used for EPI benefits. The final salary system was abolished during the 1986 reform. Public employee criticism over “Amakudari” led to further civil service employee remuneration reform in 2005. In 2007, the Social Insurance Agency pension record scandal led to a change of government by 2009. The biggest reform of the MAA pension system was the abolishment of the occupational portion of the pension, a compromise between the government and unions. We project that this compromise will cost 22 trillion yen over 90 years old. After 2055, the newly established MAA pension scheme will be abolished; thus the public pension may finally be sustainable.

Background Human herpesvirus 6 (HHV-6) encephalitis is a known life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, few studies have focused on the occurrence of HHV-6 encephalitis in patients receiving mycophenolate mofetil (MMF) combined with a calcineurin inhibitor as prophylaxis for graft-versus-host disease (GVHD). This study aimed to investigate the impact of MMF administered for GVHD prophylaxis in the occurrence of HHV-6 encephalitis after allo-HSCT and the characteristics of this condition. Methods and results We retrospectively analyzed 73 patients who underwent allo-HSCT (83 transplants) at our hospital between April 2010 and December 2015. MMF (2-3 g/d) was administered along with a calcineurin inhibitor. Seven patients (8.0%) developed encephalitis due to HHV-6. The median period from allo-HSCT to the onset of HHV-6 encephalitis was 23 days (range, 17-98 days). The cumulative incidence of HHV-6 encephalitis on day 100 after treatment was 12% and 6% in patients who underwent cord blood transplantation (CBT) and non-CBT (ie, bone marrow transplantation and peripheral blood stem cell transplantation), respectively (P = 0.344). Neurological symptoms of encephalitis were more severe in non-CBT cases than those in CBT cases. All patients diagnosed with HHV-6 encephalitis were treated with ganciclovir or foscarnet. None of the enrolled patients died from HHV-6 encephalitis. Conclusions Mycophenolate mofetil may have the potential to increase the frequency of severe HHV-6 encephalitis in patients undergoing CBT and non-CBT. Thus, MMF should be administered with caution, and patients should be monitored closely for HHV-6 encephalitis even those who did not undergo CBT.

Background In T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), activating mutations of NOTCH1 are observed in more than 50% of cases, whereas the t(7;9)(q34;q34) involving NOTCH1 at 9q34 and TRB@ at 7q34 is an extremely rare but recurrent translocation. Patient A 41-year-old male with a large mediastinal mass, pleural effusion, and lymphadenopathy was diagnosed as having T-LBL. Lymphoma cells were positive for CD4, CD8, CD2, CD3, CD5, CD7, CD10, and TdT. Results G-banding and spectral karyotyping of pleural effusion cells showed 47,XY,dup(1)(q21q32),t(7;9)(q34;q34),+20. Genomic polymerase chain reaction (PCR) revealed that the 5' end of TRB@ J1-5 was connected with the middle of NOTCH1 exon 25 (434 bp downstream from its 5' end) in a 'head-to-head' configuration on the der(9)t(7;9), although nine extra bases were inserted between the two genes. Reverse transcription-PCR confirmed expression of the TRB@/NOTCH1 fusion transcripts. Similarly, the 5' end of J1-5 was fused to the shortened exon 25 with nine extra bases. The NOTCH1 breakpoint in exon 25 was very close to transcription start sites of deleted Notch1 in murine T-ALL. Conclusions The TRB@/NOTCH1 fusion gene with a NOTCH1 breakpoint in exon 25, which has not previously been detected in four other reported cases with t(7;9), could lead to aberrant expression of the truncated NOTCH1 by TRB@ enhancer elements. The resultant NOTCH1 receptor deleting most of the extracellular domain may be implicated in the pathogenesis of T-LBL by ligand-independent, constitutive activation of the NOTCH1 pathway, suggesting avenues for future therapy with γ-secretase inhibitors.

Objectives: The t(9;11)(p22;p15) is a very rare but recurrent translocation in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) blast crisis. The translocation results in a fusion gene between NUP98 at 11p15 and PSIP1 encoding two transcriptional coactivators, p52 and p75, at 9p22. Here, we describe the first case of myelodysplastic syndrome (MDS) with t(9;11)(p22;p15). Patient: A 64-yr-old woman presented pancytopenia, trilineage dysplasia, and 9.2% blasts in the bone marrow, indicating the diagnosis of MDS. Results: G-banding and spectral karyotyping showed 46,XX,t(9;11)(p22;p15)[20]. Reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing detected four types of NUP98/PSIP1-p52 and two types of NUP98/PSIP1-p75 fusion transcripts. Essentially, the NUP98 exon 12 or exon 11 by alternative splicing was fused in-frame with the PSIP1 exon 8. Real-time quantitative (RQ) PCR for NUP98/PSIP1/GAPDH demonstrated a 4-log decrease after cord blood transplantation and a 2-log increase at relapse. Conclusions: The fusion genes combining NUP98 exon 11/12 with PSIP1 exon 8, which have never been detected in other AML/CML cases, may be implicated in the pathogenesis of MDS. Furthermore, RQ-PCR for NUP98/PSIP1 could be useful to monitor minimal residual disease.

A one-year, four month-old boy who had suffered from Kawasaki disease died suddenly during convalescence despite intensive gamma-globulin treatment. Autopsy revealed a) sausage-like aneurysms of the left and right coronary arteries and fresh thrombosis in the right coronary aneurysm, b) fresh transmural myocardial necrosis in the whole wall of the left ventricle and the anterior part of the wall of the right ventricle, and c) swelling of the cervical lymph nodes and thymus (60 g). Histologically, fibrocellular thickening of the intima and destruction of the media and internal elastic lamina were conspicuous in the area of the aneurysm, but those of the intima and media in the areas adjacent to the aneurysm were mild. Abrupt narrowing of the lumen at the border between the aneurysm and periphery of the right coronary artery was detected, and this may have been responsible for formation of the thrombus in the right coronary aneurysm. In the systemic arteries, perivascular fibrosis was very noticeable despite less severe injury to the intima and media. These findings suggest that severe inflammation of the periarterial regions was present in the acute phase. The lymph system still showed inflammation, supporting the infectious or toxic nature of Kawasaki disease.

The TRAP220 subunit of the thyroid hormone receptor-associated polypeptide transcription coactivator complex (TRAP/Mediator complex), mammalian counterpart of the yeast Mediator complex, is proposed to act on a variety of major and specific biological events through physical interactions with nuclear receptors. The vitamin D receptor (VDR) and retinoic acid receptor (RAR), coupled with retinoid X receptor (RXR), are nuclear receptors which have important roles for monopoiesis and granulopoiesis, respectively. In this study, we present the functional role of TRAP220 in nuclear receptor-mediated monopoiesis and granulopoiesis. The mouse Trap220−/– yolk sac hematopoietic progenitor cells were resistant to 1,25-dihydroxyvitamin D3-stimulated differentiation into monocytes/macrophages. Furthermore, flow cytometric analyses showed that HL-60 cells, human promyelocytic leukemia cell line, wherein TRAP220 was down-regulated, did not differentiate efficiently into monocytes and granulocytes by stimulation with 1,25-dihydroxyvitamin D3 and all-trans retinoic acid, correspondingly. The expression of direct target genes of VDR or RAR, as well as the differentiation marker genes, was low in the knockdown cells. These results indicated a crucial role of TRAP220 in the optimal VDR- and RAR-mediated myelomonocytic differentiation processes in mammalian hematopoiesis.

The Philadelphia (Ph) chromosome is observed in approximately 1% of patients with acute myeloblastic leukaemia (AML), especially subtypes M1 and M2 in the French-American-British classification. We describe here a cytogenetic and molecular investigation of a rare case with Ph-positive AML M6 (erythroleukaemia). A 63-yr-old woman was diagnosed as having erythroleukaemia. Leukaemic cells were positive for CD4 and CD7 as well as CD13, CD33, CD34 and HLA-DR. They were analyzed by G-banding, fluorescence in situ hybridization (FISH), Southern blot and reverse transcriptase polymerase chain reaction analyses. The karyotypes at diagnosis were as follows: 61, XX, -X, -1, -2, -3, -4, -5, -7, t(9;22)(q34;q11)x 2, -15, -16, -17, -18, + 19, +21, +22 [3]/61, idem, -22, +der(22)t(9;22) [36]. FISH with BCR/ABL probes showed that 39% and 57% of interphase nuclei had double and triple BCR/ABL fusion signals, respectively. Chromosome analysis in complete remission showed a normal karyotype in all 20 metaphases, confirming the diagnosis as Ph positive-acute leukaemia. FISH at relapse showed that 92% of interphase nuclei had triple fusion signals. Rearrangement of major breakpoint cluster region (M-bcr) in the BCR gene and coexpression of p210-type (b2a2) and p190-type (e1a2) BCR/ABL fusion transcripts due to alternative splicing were also detected. We conclude that clonal evolution from double to triple Ph chromosomes may be implicated in the disease progression. Considering other two reported cases, Ph-positive erythroleukaemia appears to be correlated with coexpression of myeloid/T-lymphoid markers and hyperdiploidy with double or triple Ph chromosomes, although breakpoints in the BCR gene are heterogenous.

The t(7;11)(p15;p15) translocation is a recurrent aberration observed in acute myeloblastic leukaemia (AML) and chronic myelogenous leukaemia (CML). It has been shown that the NUP98 gene at 11p15 is fused with the HOXA9 gene at 7p15 in AML with t(7;11). We report the first case with CML expressing the NUP98/HOXA9 fusion transcript. A 27-year-old Japanese man was initially diagnosed as in the chronic phase of Philadelphia-positive CML. At the diagnosis of myeloid blast crisis, the karyotype evolved to 46, XY, t(7;11)(p15;p15), t(9;22)(q34;q11). Reverse transcriptase polymerase chain reaction identified the NUP98/HOXA9 transcript, suggesting that the NUP98/HOXA9 fusion protein could play a critical role in the progression to blast crisis.

Translocation t(6;9)(p23;q34), resulting in a dek-can gene fusion, is a recurrent chromosomal abnormality mainly associated with specific subtypes of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). Patients with this type of chromosomal change are usually young and their prognosis is poor. The role of fusion protein generated from dek-can chimaeric transcript on the leukaemogenesis of t(6;9) AML or MDS is as yet unknown. We have established the first permanent cell line (FKH-1) with t(6;9), derived from the peripheral blood of a patient with t(6;9) AML transformed from Philadelphia chromosome (Ph1)-negative chronic myelocytic leukaemia (CML). The FKH-1 expressed myelomonocytic markers and dek-can chimaeric transcript. In the presence of 10 ng/ml recombinant human granulocyte colony-stimulating factor (G-CSF), the cells doubled every 54 h and showed multilineage myeloid differentiation, resulting in heterogenous morphologies such as macrophages, basophils, eosinophils and neutrophils. Thus, this cell line may be derived from a pluripotent myeloid stem cell and should be a useful tool for biomolecular studies on the pathogenesis of t(6;9) myeloid malignancies which have rarely been investigated because of the lack of continuously proliferating cells.

Trisomy 11 as a sole chromosomal abnormality is a rare aberration observed in myelodysplastic syndrome (MDS) or acute myeloblastic leukemia (AML). Recently a partial tandem duplication of the MLL gene, located on chromosome band 11q23, has been identified in de novo AML with trisomy 11. We describe a 72-year-old woman suffering from MDS-derived overt leukemia with trisomy 11 and a tandem duplication of the MLL gene. At first the patient was found to have myeloblasts with Auer rods in the peripheral blood and diagnosed as MDS, refractory anemia with excess of blasts in transformation (RAEB-T). After 2 months a picture of overt leukemia (AML; M2) developed as shown by an increased number of myeloblasts. Various chemotherapy regimens had little effect, and she died of disease progression 15 months after admission. During her clinical course, the chromosome analyses consistently showed 47,XX, +11. Southern blot analysis of leukemic blasts on admission and in accelerated phase revealed identical rearranged bands of the MLL gene. Fluorescence in situ hybridization analysis excluded the possibility of masked translocation of the MLL gene to other chromosomes. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis using a forward exon 6 primer and a backward exon 3 primer demonstrated an in-frame fusion of exon 8 with exon 2. Our results indicated that a partial tandem duplication of exons 2-8 of the MLL gene could be observed in MDS-derived overt leukemia as well as de novo AML with trisomy 11.

An 8 year old girl with acute disseminated encephalomyelitis (ADEM) is described. Elevated serum antibody titers suggested recent Mycoplasma pneumoniae infection. T2-weighted image of magnetic resonance imaging (MRI) disclosed multiple lesions of high signal intensity in bilateral basal ganglia and thalami as well as in the white matter. Postcontrast T1-weighted image revealed an enhanced lesion in the deep white matter. She showed rapid clinical improvement in response to corticosteroid therapy. The lesions had disappeared completely on MRI performed 10 weeks after the onset. ADEM is believed to be a demyelinating disorder of probable autoimmune etiology. MRI findings in this case may support the hypothesis that the primary pathological event is vascular injury and demyelination occurs only as a secondary phenomenon.

A total of 370 children who underwent upper gastrointestinal endoscopy (534 procedures) were retrospectively studied. All procedures were performed successfully. Side effects were demonstrated in only one case (0.2%), which was complicated by perioral cyanosis during the procedure. As to pre-endoscopic medication, it was thought that topical pharyngeal anesthesia alone may well be used for school-age children over 7 years of age, general anesthesia with endotracheal intubation for neonates, and intravenous sedation for infants and younger children. Of 370 patients studied, 70.8% had endoscopic diagnoses. The most common diagnosis was gastritis (136 cases), followed by peptic ulcer (75), duodenitis (29), and esophagitis (20). Several conclusions for indications were drawn from the present study. Pediatric upper gastrointestinal endoscopy is a safe and useful method for diagnostic and therapeutic approach, if adequate pre-endoscopic medication is chosen.

Purpose: Attention has recently been directed to pediatric cases of a peculiar type of postencephalitic or encephalopathic epilepsy proposed by Awaya et al. This type is characterized by an abrupt onset of frequent refractory complex partial seizures followed by the development of partial epilepsy. There is no seizure-free interval, and the seizure-type is fundamentally the same as that in the acute phase. Therefore, it is hard to distinguish the encephalitis/encephalopathy-related seizures from epileptic ones as its sequela. The pathomechanism of this syndrome remains unknown, even though viral infection has been postulated. After studying our cases, we looked for those in this category to elucidate its clinical characteristics. Methods: Five cases (two boys and three girls) with this syndrome were selected for this study from 53 pediatric patients with acute encephalopathy or encephalitis. These patients had been treated at Sendai City Hospital during the years from 1986 to 1996. This is an incidence of 9.4%. Clinical features such as cerebrospinal fluid and EEG findings, neuroimaging, prognosis of epileptic seizures, and mental status were investigated. Results: The age at onset ranged from 4 to 14 years. All cases had no significant previous or family history. In all cases, there was an antecedent infection. Seizure type during the acute phase consisted of complex partial seizures with or without secondarily generalized tonic-clonic convulsions. All had a high fever during the acute stage. The interictal EEG revealed generalized high-voltage slow waves, and the ictal EEG showed diffuse spike-and-wave discharges developing from temporal or occipital spike foci. Mild cerebrospinal fluid pleocytosis was noted in two cases. The five cases were divided into two groups according to their clinical severity. In the severe group (three cases), the seizures during the acute phase were highly refractory. Pentobarbital (PTB) was administered to two of the three cases. The duration of the acute phase ranged from 1 to 5 months. The computed tomography (CT) and magnetic resonance imaging (MRI) showed diffuse cerebral atrophy. In one case, localized lesions also were detected in the right temporal and both occipital lobes. The lesions coincided with EEG spike foci, which persisted throughout the course. All three had profound mental deterioration and intractable partial epilepsy during the chronic phase. On the other hand, in the mild group (two cases), seizures during the acute phase were suppressed by intravenous midazolam (MDL) or lidocaine. The duration of the acute phase was shorter (12 and 24 days). Neither MRI abnormalities nor mental deterioration was observed. Epileptic seizures after the convalescent phase were rare. Conclusions: Among the three severe cases, one corresponded well to Awaya's description, and the others appeared to be more severe. The mild group apparently showed less severity. After reviewing the literature, previously reported patients were no less severe than Awaya's original cases. Therefore it is noteworthy that the two milder cases might indicate that this syndrome has a wider clinical spectrum than previously suspected. The pathogenesis of the disorder could not be clarified by this study. However, after judging the focal brain lesions detected on the MRI in one case, the focal encephalitic process and localization-related epilepsy as its sequela might offer a partial explanation for the pathogenesis of this disorder.